The anemic Friend virus gp55 envelope protein induces erythroid differentiation in fetal liver colony-forming units-erythroid.
The gp55 envelope proteins of the spleen focus-forming virus initiate erythroleukemia in adult mice. Because the gp55 from the polycythemic strain (gp55-P), but not from the anemic strain (gp55-A), activates the erythropoietin receptor (EpoR) for proliferation of hematopoietic cell lines, the mechanism by which gp55-A initiates erythroleukemia has remained a mystery. We show here that gp55-A activates the EpoR in fetal liver cells. In contrast to previous studies using bone marrow cells from phenylhydrazine-treated, anemic mice, we find that both gp55-A and gp55-P induce erythroid differentiation from colony-forming unit-erythroid (CFU-E) progenitors in fetal liver cells. The effects on CFU-Es of both gp55-A and -P are mediated by the EpoR, because no colonies are seen upon expression of either gp55 in EpoR-/- fetal liver cells. However, only gp55-P induces erythroid bursts from burst-forming unit-erythroid progenitors and only gp55-P induces Epo independence in Epo-dependent cell lines. Using chimeric gp55 P/A proteins, we extend earlier work showing that the transmembrane sequence determines the capacity of gp55 proteins to differentially activate EpoR signaling. We discuss the possibilities for different signaling capacities of gp55-A and -P in fetal liver and bone marrow-derived erythroid progenitor cells.
Constantinescu
S N
SN
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Wu
H
H
Liu
X
X
Beyer
W
W
Fallon
A
A
Lodish
H F
HF
D000818:Animals; D004920:Erythropoiesis / Q000502:physiology*; D005260:Female; D005622:Friend murine leukemia virus / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D008099:Liver / Q000166:cytology* / Q000196:embryology / Q000502:physiology; D051379:Mice; D011247:Pregnancy; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D014759:Viral Envelope Proteins / Q000502:physiology*
D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; C078780:glycoprotein gp55, Friend spleen focus-forming virus